Gastroenterology

Colonization of the infant gut by microorganisms over the first year of life is crucial for development of a balanced immune response. Early alterations in the gastrointestinal microbiota of neonates has been linked with subsequent development of asthma and atopy in older children. Here we describe high-resolution culture-independent analysis of stool samples from 6month old infants fed daily supplements of Lactobacillus casei subsp. Rhamnosus (LGG) or placebo in a double-blind, randomized Trial of Infant Probiotic Supplementation (TIPS). Bacterial community composition was examined using a highdensity microarray, the 16S rRNA PhyloChip, and the microbial assemblages of infants with either high or low LGG abundance were compared. Communities with high abundance of LGG exhibited promotion of phylogenetically clustered taxa including a number of other known probiotic species, and were significantly more even in their distribution of community members. Ecologically, these aspects are characteristic of communities that are more resistant to perturbation and outgrowth of pathogens. PhyloChip analysis also permitted identification of taxa negatively correlated with LGG abundance that have previously been associated with atopy, as well as those positively correlated that may prove useful alternative targets for investigation as alternative probiotic species. From these findings we hypothesize that a key mechanism for the protective effect of LGG supplementation on subsequent development of allergic disease is through promotion of a stable, even, and functionally redundant infant gastrointestinal community. Citation: Cox MJ, Huang YJ, Fujimura KE, Liu JT, McKean M, et al. (2010) Lactobacillus casei Abundance Is Associated with Profound Shifts in the Infant Gut Microbiome. PLoS ONE 5(1): e8745.

Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective ''early'' and ''late'' colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.

RATIONALE: Viral wheezing illnesses in early childhood have been shown to predict development of asthma by 6 years of age. Whether a differential effect on the risk for persistence of asthma out to age 11 years exists based on viral etiology of early childhood wheezing illnesses has not been established. METHODS: 217 children were followed prospectively from birth to 11 years in the COAST (Childhood Origins of ASThma) study. The etiology of viral wheezing illnesses during early childhood was determined using nasal lavage, culture and RT-PCR. Asthma was diagnosed clinically at 11 years. Relationships between the etiology of wheezing illnesses and asthma risk were analyzed. RESULTS: In univariate analyses, wheezing illnesses in the first 3 years of life with HRV (OR56.0 95% CI 2.1, 11, p<0.0001), RSV (OR52.9 95% CI 1.6, 5.4, p50.0008) and other viruses (OR54.8 95% CI 2.6, 9.1, p<0.0001) were all associated with an increased risk of asthma at age 11. Using a multivariate model to adjust for histories of wheezing with more than one virus, the risk of asthma at age 11 years was significantly increased in children with HRV wheezing histories (OR53.7 95% CI 1.7, 7.8, p50.0008), but not in children who wheezed with RSV (OR51.4 95% CI 0.7, 2.9, p50.4) or other viruses (OR52.1 95% CI 0.9, 4.7, p50.08). CONCLUSIONS: Viral etiology of wheezing illnesses in the first three years of life confers a differential risk for persistent asthma out to 11 years of age with wheezing due to HRV being the strongest overall predictor of this development. RATIONALE: Our aim was to describe the prevalence and severity of wheezing in the first year of life among infants with low birth weight (BW). METHODS: Answers from 9833 parents living in six different cities of Brazil to the International Study of Wheezing in Infants (EISL) questionnaire were analyzed. 674 infants were born with low BW and were separated in two groups according to the weight at birth: group A (2000g to 2499g; N5499) and B (<2000g; N5175). RESULTS: Compared to infants with normal BW (N59159) those with low BW (groups A and B) had higher prevalence of recurrent wheezing (18% vs 28% and 44%, respectively; p<0.0001), hospitalization due to wheezing (8% vs 11% and 23%; p<0.01) and severe wheezing (8% vs 19% e 33%; p<0.0001). Medical diagnosis of asthma was more frequently observed only among infants in the group B (7% vs 17%; p<0.0001). Infants in the group B had significantly higher prevalence of recurrent wheezing, hospitalization due to wheezing, severe wheezing and medical diagnosis of asthma than those in group A. CONCLUSIONS: Infants with low BW showed a clear higher wheezing related morbidity in the first year of life. An inverse association was noted between BW and its impact on respiratory outcomes. RATIONALE: To understand the relationship between microbial exposure, asthma and allergy, analysts need new tools that facilitate intuitive exploration of complex multivariate data.

Background: Wheezing illnesses cause major morbidity in infants and are frequent precursors to asthma. Objective: We sought to examine environmental factors associated with recurrent wheezing in inner-city environments. Methods: The Urban Environment and Childhood Asthma study examined a birth cohort at high risk for asthma (n 5 560) in Baltimore, Boston, New York, and St Louis. Environmental assessments included allergen exposure and, in a nested case-control study of 104 children, the bacterial content of house dust collected in the first year of life. Associations were determined among environmental factors, aeroallergen sensitization, and recurrent wheezing at age 3 years. Results: Cumulative allergen exposure over the first 3 years was associated with allergic sensitization, and sensitization at age 3 years was related to recurrent wheeze. In contrast, first-year exposure to cockroach, mouse, and cat allergens was negatively associated with recurrent wheeze (odds ratio, 0.60, 0.65, and 0.75, respectively; P < _ .01). Differences in house dust bacterial content in the first year, especially reduced exposure to specific Firmicutes and Bacteriodetes, was associated with atopy and atopic wheeze. Exposure to high levels of both allergens and this subset of bacteria in the first year of life was most common among children without atopy or wheeze. Conclusions: In inner-city environments children with the highest exposure to specific allergens and bacteria during their first year were least likely to have recurrent wheeze and allergic sensitization. These findings suggest that concomitant exposure to high levels of certain allergens and bacteria in early life might be beneficial and suggest new preventive strategies for wheezing and allergic diseases. (J Allergy Clin Immunol 2014;nnn:nnn-nnn.)